PEP-FOLD4: a pH-dependent force field for peptide structure prediction in aqueous solution

Rey, Julien; Murail, Samuel; Vries, Sjoerd de; Derreumaux, Philippe; Tufféry, Pierre

doi:10.1093/nar/gkad376

Cited by 37 publications

(14 citation statements)

References 45 publications

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“…Notably, most of the generated data (77.7%) exhibited a sequence identity with the training data above 50% outperforming HelixGAN (Figure 2E and Figure S2). We then compared the structural similarity of HelixDiff's α right-handed helix structures to PEP-FOLD4, 18 a commonly used algorithm for predicting peptide 3D structures. For a small random sample of sequences, we found a strong resemblance between the structures generated by both techniques (Figure S3).…”

Section: ■ Resultsmentioning

confidence: 99%

HelixDiff, a Score-Based Diffusion Model for Generating All-Atom α-Helical Structures

Xie,

Valiente,

Kim

et al. 2024

ACS Cent. Sci.

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Here, we present HelixDiff, a score-based diffusion model for generating all-atom helical structures. We developed a hot spot-specific generation algorithm for the conditional design of α-helices targeting critical hotspot residues in bioactive peptides. HelixDiff generates α-helices with near-native geometries for most test scenarios with root-mean-square deviations (RMSDs) less than 1 Å. Significantly, HelixDiff outperformed our prior GANbased model with regard to sequence recovery and Rosetta scores for unconditional and conditional generations. As a proof of principle, we employed HelixDiff to design an acetylated GLP-1 Dpeptide agonist that activated the glucagon-like peptide-1 receptor (GLP-1R) cAMP accumulation without stimulating the glucagonlike peptide-2 receptor (GLP-2R). We predicted that this Dpeptide agonist has a similar orientation to GLP-1 and is substantially more stable in MD simulations than our earlier D-GLP-1 retro-inverse design. This D-peptide analogue is highly resistant to protease degradation and induces similar levels of AKT phosphorylation in HEK293 cells expressing GLP-1R compared to the native GLP-1. We then discovered that matching crucial hotspots for the GLP-1 function is more important than the sequence orientation of the generated D-peptides when constructing D-GLP-1 agonists.

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Section: ■ Resultsmentioning

confidence: 99%

HelixDiff, a Score-Based Diffusion Model for Generating All-Atom α-Helical Structures

Xie,

Valiente,

Kim

et al. 2024

ACS Cent. Sci.

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“…Peptide structure files were obtained by the online peptide structure constructor (). 20 The reaction system was constructed using Gromacs 2022.3 software. The Charmm36 force field and TIP3P water model were selected and each peptide was placed in a cubic box.…”

Section: Methodsmentioning

confidence: 99%

Evaluating the capability of soybean peptides as calcium ion carriers: a study through sequence analysis and molecular dynamics simulations

An,

Wang,

et al. 2024

RSC Adv.

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“…To investigate the structural properties of the model peptides, Pen(desMet): RQIKIWFQNRRKWKK and Trp56GlyPen(desMet): RQIKIWFQNRRK G KK, we employed Pep-Fold4 that can predict peptide structures from amino acid sequences [ 50 ] to generate the initial structures of model peptides at pH 7.5 and 100 mM ionic strength. We chose the top best structure among the five best structures of model peptide ( Supporting Materials Figure S17 ).…”

Section: Methodsmentioning

confidence: 99%

Influence of Aza-Glycine Substitution on the Internalization of Penetratin

Tarchoun,

Soltész,

Farkas

et al. 2024

Pharmaceutics

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The cell-penetrating peptide (CPP) penetratin has gained much attention over many years due to its potential role as a transporter for a broad range of cargo into cells. The modification of penetratin has been extensively investigated too. Aza-peptides are peptide analogs in which one or more of the amino residues are replaced by a semicarbazide. This substitution results in conformational restrictions and modifications in hydrogen bonding properties, which affect the structure and may lead to enhanced activity and selectivity of the modified peptide. In this work, the Trp residues of penetratin were substituted by aza-glycine or glycine residues to examine the effect of these modifications on the cellular uptake and the internalization mechanism. The substitution of Trp48 or Trp48,56 dramatically reduced the internalization, showing the importance of Trp48 in cellular uptake. Interestingly, while aza-glycine in the position of Trp56 increased the cellular uptake, Gly reduced it. The two Trp-modified derivatives showed altered internalization pathways, too. Based on our knowledge, this is the first study about the effect of aza-amino acid substitution on the cell entry of CPPs. Our results suggest that aza-amino acid insertion is a useful modification to change the internalization of a CPP.

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PEP-FOLD4: a pH-dependent force field for peptide structure prediction in aqueous solution

Cited by 37 publications

References 45 publications

HelixDiff, a Score-Based Diffusion Model for Generating All-Atom α-Helical Structures

HelixDiff, a Score-Based Diffusion Model for Generating All-Atom α-Helical Structures

Evaluating the capability of soybean peptides as calcium ion carriers: a study through sequence analysis and molecular dynamics simulations

Influence of Aza-Glycine Substitution on the Internalization of Penetratin

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